This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.Aims
Methods
A novel injectable hydrogel based on DNA and silicate nanodisks was fabricated and optimized to obtain a suitable drug delivery platform for biomedical applications. Precisely, the hydrogel was designed by combining two different type of networks: a first network (type A) made of interconnections between neighboring DNA strands and a second one (type B) consisting of electrostatic interactions between the silicate nanodisks and the DNA backbone. The silicate nanodisks were introduced to increase the viscosity of the DNA physical hydrogel and improve their shear-thinning properties. Additionally, the silicate nanodisks were selected to modulate the release capability of the designed network. DNA 4% solutions were heated at 90°C for 45 seconds and cooled down at 37°C degree for two hours. In the second step, the silicate nanodisks suspension in water at different concentrations (0.1 up to 0.5%) were then mixed with the pre-gel DNA hydrogels to obtain the nanocomposite hydrogels. Rheological studies were carried out to investigate the shear thinning properties of the hydrogels. Additionally, the hydrogels were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron microscopy. The hydrogels were loaded with the osteoinductive drug dexamethasone and its release was tested in vitro in phosphate buffer pH 7.4. The drug activity upon release was tested evaluating the osteogenic differentiation of human adipose derived stem cells (hASCs) in vitro through analysis of main osteogenic markers and quantification of alkaline phosphatase activity and calcium deposition. Finally, the hydrogels were tested in vivo and injected into cranial defects in rats to assess their biocompatibility and bone regeneration potential. The inclusion of the silicate nanodisks increased the viscosity of the hydrogels and the best results were obtained with the highest concentration of the nanoclay (0.5%). The hydrogels possessed shear-thinning properties as demonstrated by cyclic strain sweep tests and were able to recover their original storage modulus G' upon removal of strain. Such improvement in the injectable properties of the formulated hydrogels was mainly attributed to the formation of electrostatic interactions between the silicate nanodisks and the phosphate groups of the DNA backbone as confirmed by XPS analysis of the O, N, and P spectra. Additionally, laponite was able to sustain the release of the osteoinductive drug dexamethasone which was instead completely released from the DNA-based hydrogels after a week. The drug after being released was still active and promoted the osteogenic differentiation of hASCs as confirmed by ALP expression and expression of main osteogenic markers including ALP and COLA1. Finally, the gels proved to be biocompatible in vivo when injected into cranial defects and promoted bone formation at the periphery of the defect after a month post-treatment. A novel injectable shear-thinning DNA-based hydrogel was characterized and tested for its drug delivery properties. The hydrogel can promote the sustain release of a small molecule like dexamethasone and be biocompatible in vitro and in vivo. Due to these promising findings, the designed system could find also applicability for the delivery of growth factors or other therapeutic molecules.
Previous study reported that intra-articular injection of MgSO4 could alleviate pain related behaviors in a collagenase induced OA model in rats. It provided us a good description on the potential of Mg2+ in OA treatment. However, the specific efficiency of Mg2+ on OA needs to be further explored and confirmed. The underlying mechanisms should be elucidated as well. Increasing attention has been paid on existence of synovial fluid MSCs (SF-MSCs) (not culture expanded) which may participate in endogenous reparative capabilities of the joint. On the other hand, previous studies demonstrated that Mg2+ not only promoted the expression of integrins but also enhanced the strength of fibronectin-integrin bonds that indicated the promotive effect of Mg2+ on cell adhesion, moreover, Mg2+ was proved could enhance chondrogenic differentiation of synovial membrane derived MSCs by modulating integrins. Based on these evidence, we hypothesize herein intra-articular injection of Mg2+ can attenuate cartilage degeneration in OA rat through modulating the biological behavior of SF-MSCs. Human and rat SF-MSCs were collected after obtaining Experimental Ethics approval. The biological behaviors of both human and rat SF-MSCs including multiple differentiation, adhesion, colony forming, proliferation, etc. were determined in vitro in presence or absence of Mg2+ (10 mmol/L). Male SD rats (body weight: 450–500 g) were used to establish anterior cruciate ligament transection and partial medial meniscectomy (ACLT+PMM) OA models. The rats received ACLT+PMM were randomly divided into saline (control) group and MgCl2 (0.5 mol/L) group (n=6 per group). Intra-articular injection was performed on week 4 post-operation, twice per week for two weeks. Knee samples were harvested on week 2, 4, 8, 12 and 16 after injection for histological analysis for assessing the progression of OA. On week 2 and 4 after injection, the rat SF-MSCs were also isolated before the rats were sacrificed for assessing the abilities of chondrogenic differentiation, colony forming and adhesion in vitro. Statistical analysis was done using Graphpad Prism 6.01. Unpaired t test was used to compare the difference between groups. Significant difference was determined at P < 0 .05. The adhesion and chondrogenic differentiation ability of both human and rat SF-MSCs were significantly enhanced by Mg2+ (10 mmol/L) supplementation in vitro. However, no significant effects of Mg2+ (10 mmol/L) on the osteogenic and adipogenic differentiation as well as the colony forming and proliferation. In the animal study, histological analysis by Saffranin O and Toluidine Blue indicated the cartilage degeneration was significantly alleviated by intra-articular injection of Mg2+, in addition, the expression of Col2 in cartilage was also increased in MgCl2 group with respect to control group indicated by immunohistochemistry. Moreover, the OARSI scoring was decreased in MgCl2 group as well. Histological analysis and RT-qPCR indicated that the chondrogenic differentiation of SF-MSCs isolated from Mg2+ treated rats were significantly enhanced compare to control group. In the current study, we have provided direct evidence supporting that Mg2+ attenuated the progression of OA. Except for the effect of Mg2+ on preventing cartilage degeneration had been demonstrated in this study, for the first time, we demonstrated the promoting effect of Mg2+ on adhesion and chondrogenic differentiation of endogenous SF-MSCs within knee joint that may favorite cartilage repair. We have confirmed that the anti-osteoarthritic effect of Mg2+ involves the multiple actions which refer to prevent cartilage degeneration plus enhance the adhesion and chondrogenic differentiation of SF-MSCs in knee joint to attenuate the progression of OA. These multiple actions of Mg2+ may be more advantage than traditional products. Besides, this simple, widely available and inexpensive administration of Mg2+ has the potential on reducing the massive heath economic burden of OA. However, the current data just provided a very basic concept, the exact functions and underlying mechanisms of Mg2+ on attenuating OA progression still need to be further explored both in vitro and in vivo. Formula of Mg2+ containing solution also need to be optimized, for example, a sustained and controlled release delivery system need to be developed for improving the long-term efficacy.
Patellar fractures account for approximately 1% of all fractures. Open reduction and internal fixation is recommended to restore extensor continuity and articular congruity. However, complications such as nonunion and symptomatic hardware, still exist. Furthermore, there is a risk of re-fracturing of the healed bone during the removal of the implants. Magnesium (Mg), a biodegradable metal, has elastic moduli and compressive yield strength that are comparable to those of natural bone. Our previous study showed that released Mg ions enhanced fracture healing. However, Mg-based implants degrade rapidly after implantation and lead to insufficient mechanical strength to support the fracture. Microarc oxidation (MAO) is a metal surface coating that reduces corrosion. We hypothesized that Mg pins, with or without MAO, would enhance fracture healing radiologically, mechanically, and histologically, while MAO would decrease degradation of Mg pins. Patellar fracture was performed on forty-eight 18-week-old female New Zealand White rabbits according to established protocol. Briefly, the patella is osteotomized transversely and a tunnel (1.1mm) was drilled longitudinally through the two bone fragments. A pin (1 mm, stainless steel, Mg, or MAO-Mg) was inserted into the tunnel. The reduced construct was stabilized with a figure-of-eight band wire (⊘ 0.6 mm stainless steel wire). Cast immobilization was applied for 6 weeks. The rabbits were euthanized at week 8 and 12 post-operation. Microarchitecture and mechanical properties of the repaired patella were analyzed with microCT and tensile testing respectively. Histological sections of the repaired patella were stained. To evaluate the effect of the MAO treatment on degradation rate of Mg pin, the volume of the Mg pins in the patella was measured with microCT. At week 8, both Mg and Mg-MAO showed higher ratio of bone volume to tissue volume (BV/TV) than the control while there was no significant different between Mg and Mg-MAO. At week 12, Control, Mg, and Mg-MAO groups showed enlarged patella when compared to the normal patella. Tissue volume (TV) and bone volume (BV) of the patella in Mg and Mg-MAO were larger than those in the Control group. However, the Control had higher ratio of bone volume to tissue volume (BV/TV), TV density, and BV density than Mg and Mg-MAO. Tensile testing showed that the mechanical properties of the repaired patella (failure load, stiffness, ultimate strength, and energy-to-failure) of Mg and Mg-MAO were higher than that of the control at both week 8 and week 12. Histological analysis showed that there was significant new bone formation in the Mg and Mg-MAO group compared with the Control group at week 8 and 12. The degradation rate of the MAO-coated Mg pins was significantly slower than those without MAO at week 8 but no significant difference was detected at week 12. Mechanical, microarchitectural, and histological assessments showed that Mg pins, with or without MAO, enhanced fracture healing of the repaired patella compared to the Control. MAO treatment enhanced the corrosion resistance of the Mg pins at the early time point.
Ankle fractures are the fourth most common fracture requiring surgical management. The deltoid ligament is considered the primary stabilizer of the ankle against a valgus force. The management of the deltoid ligament in ankle fractures is currently a controversial topic no consensus exists regarding repair in the setting of ankle fractures. The purpose of this systematic review is to examine the role and indications for deltoid ligament repair in ankle fractures. A systematic database search was conducted with Medline, Pubmed and Embase for relevant studies discussing patients with ankle fractures involving deltoid ligament rupture and repair. The papers were screened independently and in duplicate by two reviewers. Study quality was evaluated using the MINORs criteria. Data extraction included post-operative outcomes, pain, range of motion (ROM), function, medial clear space (MCS), syndesmotic malreduction and complication rates. Following title, abstract and full text screening, 10 eligible studies published between 1987 and 2017 remained for data extraction (n = 528). The studies include 325 Weber B and 203 Weber C type fractures. Malreduction rate in studies with deltoid ligament repair was 7.4% in comparison to those without repair at 33.3% (p < 0.05). Eleven (4%) of deltoid ligament repair patients returned for re-operation to have implants removed in comparison to eighty three (42%) of those without repair (p < 0.05). There was no significant difference for pain, function, ROM, MCS and complication rates (p < 0.05). The mean operating time of deltoid ligament repair groups was 20 minutes longer than non-repair groups(p < 0.05). Deltoid ligament repair offers significantly lower syndesmotic malreduction rates and reduced re-operation rates for hardware removal when performed instead of transsyndesmotic screw fixation. When compared to non-repair groups, there are no significant differences in pain, function, ROM, MCS and complication rates. Deltoid ligament repair should be considered for ankle fracture patients with syndesmotic injury, especially those with Weber C. Other alternative syndesmotic fixation methods such as suture button fixation should be explored. A large multi-patient randomized control trial is required to further examine the outcomes of ankle fracture patients with deltoid ligament repair.
Self tapping bone screw has been widely used in the fixation of Arthroplasty implants and bone graft. But the unwanted screw or driver breakage can be a direct result of excessive driving torque due to the thread cutting resistance. Previous studies showed that bone drill bit cutting rake angle was a critical factor and was inversely related to the bone cutting efficiency.1, 2, 3, 4 (Figure 1) However to date there was no data for how the rake angle could influence the performance of self tapping bone screw. The purpose of this study was to investigate the torque generated by the self tapping cortical screw in simulated bone insertion as a function of the screw tip cutting flute rake angle. Two 5 mm thick BM5166 polyurethane block were stacked together and drilled through with 2.5mm diameter holes. Five 30mm long 3.5 mm diameter Ti6AL4V alloy self tapping cortical screws with 0°rake angle cutting flutes (Figure 2) were inserted in the holes and driven by the spanner attached to the test machine (Z5.0TN/TC-A-10) with a displacement control of 3 revolutions/min and 30N constant axial loading. The screws were driven into the stacked polyurethane block for 8mm depth. The maximum driving torque was recorded. Procedure was repeated for five same screws but with 7° rake angle cutting flutes. (Figure 2) The driving torqueses were compared. Student t test was performed with confidence level of 95% was assumed.Introduction
Methods
Medial open wedge high tibial osteotomy (HTO) is a generally accepted surgical method for medial unicompartmental osteoarthritis with varus malalignment of the lower extremity. However, several authors have suggested the possibility of unintentional secondary changes during open wedge HTO, which include posterior tibial slope angle (PTS) change, tibial rotation change and medial–lateral slope change of the knee joint line, may influence knee kinematics and produce poor clinical outcomes. We sought to analyze postoperative changes in three-dimensional planes using a virtual wedge osteotomy 3D model. Pre- and post-operative changes in the medial proximal tibial angle (MPTA) in the coronal plane, posterior tibial slope (PTS) in the sagittal plane, and axial tibial rotation were measured as dependent variables. And this study was attempted to determine their mutual relationships and to clarify which independent variables, including hinge axis angle and gap ratio, affect tibial rotation change and PTS change by applying the identified hinge position. A total of 17 patients with 19 knees underwent HTO and were evaluated with 3D-CT before and after surgery. A 3D model was constructed by applying reverse engineering software.Introduction
Method
The purpose of this study was to investigate how rim poly locking scallop cutting depth could affect the rigidity of acetabular cup. (11) generic FEA models including (5) 50mm OD Ti6Al4VELI hemispherical acetabular shells with thicknesses of 3.0, 3.5, 4.0, 4.5 and 5.0mm, and (6) 4mm thick hemispherical shells with standard rim poly indexing scallops varied in cutting depths from inner diameter of the cup in 1.0, 1.5, 2.0, 2.5, 3.0 and 3.5mm. All cups were analyzed in ANSYS® Workbench™ FEA software with a loading condition of 2000N applied to the cup rim per V15 ISO/TC 150/SC 4 N. Verification was carried out by the physical test of a same generic Ti6Al4VELI 50mmOD and 5mm thick solid hemispherical shell under 2000N rim directed load. The cup deformation was compared with FEA results. The maximum deformation of FEA scalloped cups were compared with that of solid hemispherical cups with different shell thickness.Objective
Materials and Methods
PEEK rods construct has been proposed to allow better load sharing among spinal components when compared to the more traditional Titanium rods constructs. However, such proposal has largely derived from single-load in-vitro testing and the biomechanical differences between the two constructs when subjected to fatigue loading remain unknown. Current study comparatively analyzed the in-vitro biomechanical performance of PEEK and Titanium rod constructs as spinal implants through a 5 hour fatigue loading test. The disc height and intradiscal pressure of the instrumented and adjacent levels pre- and post-loading were recorded for analysis. The stress levels on the rods and bone stress near the screw-bone interface were also collected to investigate the likely failure rates of the two constructs. The results showed that the Titanium rods construct demonstrated a minimum amount of loss of disc height and intradiscal pressure at the instrumented level, however, a significant loss of the disc height and intradiscal pressure at adjacent levels compared to the intact spine were identified. In contrast, the disc height and intradiscal pressure of the PEEK rods were found to be comparable to those of the intact spine for all levels. The PEEK rods group also showed significantly less bone stress near the screw-bone interface compared to the Titanium rods group. Current study has demonstrated the potential benefits of the PEEK rods construct in reducing the risks of adjacent segment disease and implant failure rates when compared to the more traditional Titanium rods construct.
Femoral shaft fracture treatment often results in mal-alignment and the high dosage of radiation exposure. The objective of this study is to develop a Parallel Manipulator Robot (PMR) on traction table to overcome these difficulties so as achieve better alignment for the fractured femur and reduce radiation to both patients and physicians. The distal platform of PMR is attached to the central pole on standard traction table by the boot adaptor. A leg model with soft tissue made by Pacific Research Laboratory, Inc. is flexed at the knee with patella on the top. A 2/3 circular ring, with 1/3 open circle down, fixed to the fractured distal femur with one trans-wire and one self-tapping screw, acting as adaptable stirrup fixing scheme. To secure proximal femur, an adapter is assembled on the traction table and fixed on the proximal femur. The distal femur is fixed to the 2/3 circular ring platform of PMR. Surgical planning is performed by first acquiring the bi-planar images from the C-Arm X-ray machine. After simulated fracture on 3-D femoral model is made, proximal and distal segments of the model will be superimposed with background bi-planar images. Finally the pre-fractured length and mechanical axis of 3-D femoral model will be restored. Afterwards, a table of schedule for length adjustments of six struts of PMR is generated. This length adjustment schedule is used to drive the PMR for fractured femur alignment and reduction. When reduction completed, a special designed device is used to fix the reduced femur. Then the PMR is removed from the traction table and the patient can be removed from the traction table.Objectives
Methods
Percutaneous iliosacral screw placement is a standard, stabilization technique for pelvic fractures. The purpose of this study was to assess the effectiveness of a novel biplanar robot navigation aiming system for percutaneous iliosacral screw placement in a human cadaver model. A novel biplanar robot navigation aiming system was used in 16 intact human cadaveric pelvises for percutaneous iliosacral screw insertion. The number of successful screw placements and mean time for this insertion and intra-operative fluoroscopy per screw-pair were recorded respectively to evaluate the procedure. The accuracy of the aiming process was evaluated by computed tomography.Objectives
Methods
Femoral shaft fracture treatment often results in mal-alignment and the high dosage of radiation exposure. The objective of this study is to develop a Parallel Manipulator Robot (PMR) on traction table to overcome these difficulties so as achieve better alignment for the fractured femur and reduce radiation to both patients and physicians. The distal platform of PMR is attached to the central pole on standard traction table by the boot adaptor. A leg model with soft tissue made by Pacific Research Laboratory, Inc. is flexed at the knee with patella on the top. A 2/3 circular ring, with 1/3 open circle down, fixed to the fractured distal femur with one trans-wire and one self-tapping screw, acting as adaptable stirrup fixing scheme. To secure proximal femur, an adapter is assembled on the traction table and fixed on the proximal femur. The distal femur is fixed to the 2/3 circular ring platform of PMR. Surgical planning is performed by first acquiring the bi-planar images from the C-Arm X-ray machine. After simulated fracture on 3-D femoral model is made, proximal and distal segments of the model will be superimposed with background bi-planar images. Finally the pre-fractured length and mechanical axis of 3-D femoral model will be restored. Afterwards, a table of schedule for length adjustments of six struts of PMR is generated. This length adjustment schedule is used to drive the PMR for fractured femur alignment and reduction. When reduction completed, a special designed device is used to fix the reduced femur. Then the PMR is removed from the traction table and the patient can be removed from the traction table.Objective
Method